The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors.

Autor:	Alemasova EE; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia., Naumenko KN; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia.; Novosibirsk State University, Novosibirsk, 630090, Russia., Kurgina TA; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia.; Novosibirsk State University, Novosibirsk, 630090, Russia., Anarbaev RO; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia.; Novosibirsk State University, Novosibirsk, 630090, Russia., Lavrik OI; Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences (SB RAS), Novosibirsk, 630090, Russia.; Novosibirsk State University, Novosibirsk, 630090, Russia.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2018 May 04; Vol. 9 (34), pp. 23349-23365. Date of Electronic Publication: 2018 May 04 (Print Publication: 2018).
DOI:	10.18632/oncotarget.25158
Abstrakt:	Y-box-binding protein 1 (YB-1) is a multifunctional cellular factor overexpressed in tumors resistant to chemotherapy. An intrinsically disordered structure together with a high positive charge peculiar to YB-1 allows this protein to function in almost all cellular events related to nucleic acids including RNA, DNA and poly(ADP-ribose) (PAR). In the present study we show that YB-1 acts as a potent poly(ADP-ribose) polymerase 1 (PARP1) cofactor that can reduce the efficiency of PARP1 inhibitors. Similarly to that of histones or polyamines, stimulatory effect of YB-1 on the activity of PARP1 was significantly higher than the activator potential of Mg 2+ and was independent of the presence of EDTA. The C-terminal domain of YB-1 proved to be indispensable for PARP1 stimulation. We also found that functional interactions of YB-1 and PARP1 can be mediated and regulated by poly(ADP-ribose). Competing Interests: CONFLICTS OF INTEREST The authors declare that there is no conflict of interest in this work.
Databáze:	MEDLINE
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